Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), which are caused by coronaviruses, have attracted substantial attention owing to their high mortality rates and potential to cause epidemics. Yuen and colleagues discuss progress with treatment options for these syndromes, including virus- and host-targeted drugs, and the challenges that need to be overcome in their further development. In humans, infections with the human coronavirus (HCoV) strains HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1 usually result in mild, self-limiting upper respiratory tract infections, such as the common cold. By contrast, the CoVs responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), which were discovered in Hong Kong, China, in 2003, and in Saudi Arabia in 2012, respectively, have received global attention over the past 12 years owing to their ability to cause community and health-care-associated outbreaks of severe infections in human populations. These two viruses pose major challenges to clinical management because there are no specific antiviral drugs available. In this Review, we summarize the epidemiology, virology, clinical features and current treatment strategies of SARS and MERS, and discuss the discovery and development of new virus-based and host-based therapeutic options for CoV infections.

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Coronaviruses - drug discovery and therapeutic options.

Outbreaks of Middle East respiratory syndrome (MERS) raise questions about the prevalence and evolution of the MERS coronavirus (CoV) in its animal reservoir. Our surveillance in Saudi Arabia in 2014 and 2015 showed that viruses of the MERS-CoV species and a human CoV 229E-related lineage co-circulated at high prevalence, with frequent co-infections in the upper respiratory tract of dromedary camels. viruses of the betacoronavirus 1 species, we found that dromedary camels share three CoV species with humans. Several MERS-CoV lineages were present in camels, including a recombinant lineage that has been dominant since December 2014 and that subsequently led to the human outbreaks in 2015. Camels therefore serve as an important reservoir for the maintenance and diversification of the MERS-CoVs and are the source of human infections with this virus.

https://science.sciencemag.org/content/sci/351/6268/81.full.pdf

Co-circulation of three camel coronavirus species and recombination of MERS-CoVs in Saudi Arabia

The first known cases of Middle East respiratory syndrome (MERS), associated with infection by a novel coronavirus (CoV), occurred in 2012 in Jordan but were reported retrospectively. The case first to be publicly reported was from Jeddah, in the Kingdom of Saudi Arabia (KSA). Since then, MERS-CoV sequences have been found in a bat and in many dromedary camels (DC). MERS-CoV is enzootic in DC across the Arabian Peninsula and in parts of Africa, causing mild upper respiratory tract illness in its camel reservoir and sporadic, but relatively rare human infections. Precisely how virus transmits to humans remains unknown but close and lengthy exposure appears to be a requirement. The KSA is the focal point of MERS, with the majority of human cases. In humans, MERS is mostly known as a lower respiratory tract (LRT) disease involving fever, cough, breathing difficulties and pneumonia that may progress to acute respiratory distress syndrome, multiorgan failure and death in 20 % to 40 % of those infected. However, MERS-CoV has also been detected in mild and influenza-like illnesses and in those with no signs or symptoms. Older males most obviously suffer severe disease and MERS patients often have comorbidities. Compared to severe acute respiratory syndrome (SARS), another sometimes- fatal zoonotic coronavirus disease that has since disappeared, MERS progresses more rapidly to respiratory failure and acute kidney injury (it also has an affinity for growth in kidney cells under laboratory conditions), is more frequently reported in patients with underlying disease and is more often fatal. Most human cases of MERS have been linked to lapses in infection prevention and control (IPC) in healthcare settings, with approximately 20 % of all virus detections reported among healthcare workers (HCWs) and higher exposures in those with occupations that bring them into close contact with camels. Sero-surveys have found widespread evidence of past infection in adult camels and limited past exposure among humans. Sensitive, validated reverse transcriptase real-time polymerase chain reaction (RT-rtPCR)-based diagnostics have been available almost from the start of the emergence of MERS. While the basic virology of MERS-CoV has advanced over the past three years, understanding of the interplay between camel, environment, and human remains limited.

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MERS coronavirus: diagnostics, epidemiology and transmission

Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes a spectrum of respiratory illness, from asymptomatic to mild to fatal. MERS-CoV is transmitted sporadically from dromedary camels to humans and occasionally through human-to-human contact. Current epidemiologic evidence supports a major role in transmission for direct contact with live camels or humans with symptomatic MERS, but little evidence suggests the possibility of transmission from camel products or asymptomatic MERS cases. Because a proportion of case-patients do not report direct contact with camels or with persons who have symptomatic MERS, further research is needed to conclusively determine additional mechanisms of transmission, to inform public health practice, and to refine current precautionary recommendations.

/pdf/middle-east-respiratory-syndrome-coronavirus-transmission-237zfgrjjw.pdf

Middle East Respiratory Syndrome Coronavirus Transmission

Coronaviruses are one of many groups of viruses that cause the common cold, though some members of the group can cause more serious illnesses. The SARS coronavirus, for example, caused a widespread epidemic of pneumonia in 2003 that killed 774 people. In 2012, a new coronavirus was detected in patients from the Arabian Peninsula with severe respiratory symptoms known as Middle East respiratory syndrome (or MERS for short). To date the MERS coronavirus has also killed over 700 people (albeit over a number of years rather than months). Yet unlike the SARS coronavirus that spreads efficiently between humans, cases of MERS were rarely linked to each other or to contact with animals, with the exception of hospital outbreaks. Though camels were later identified as the original source of MERS coronavirus infections in humans, the role of these animals in the epidemic was not well understood. Throughout the epidemic nearly 300 genomes of the MERS coronavirus had been sequenced, from both camels and humans. Previous attempts to understand the MERS epidemic had either relied on these data or reports of case numbers but led to conflicting results, at odds with other sources of evidence. Dudas et al. wanted to work out how many times the MERS coronavirus had been introduced into humans from camels. If it happened once, this would indicate that the virus is good at spreading between humans and that treating human cases should be a priority. However, if every human case occurred as a new introduction of the MERS coronavirus from camels, this would mean that the human epidemic would not stop until the virus is controlled at the source, that is, in camels. Many scientists had argued that the second of these scenarios was most likely, but this had not been strongly demonstrated with data. By looking at the already sequenced genomes, Dudas et al. worked out how the MERS coronaviruses were related to each other, and reconstructed their family tree. Information about the host from which each sequence was collected was then mapped on the tree. Unlike previous attempts to complete this kind of analysis, Dudas et al. took an approach that could deal with the viruses in camels being more diverse than those in humans. Consistent with the scenario where human cases occurred as new introductions from camels, the analysis showed that the MERS coronavirus populations is maintained exclusively in camels and the viruses seen in humans are evolutionary dead-ends. This suggests that MERS coronavirus spreads poorly between humans, and has instead jumped from camels to humans hundreds of times since 2012. As well as providing data to confirm a previously suspected hypothesis, these findings provide more support to the current plans to mitigate infections with MERS coronavirus in the Arabian Peninsula by focusing control efforts on camels.

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MERS-CoV spillover at the camel-human interface.

Camels carry Middle East respiratory syndrome coronavirus, but little is known about infection age or prevalence. We studied >800 dromedaries of all ages and 15 mother–calf pairs. This syndrome constitutes an acute, epidemic, and time-limited infection in camels <4 years of age, particularly calves. Delayed social separation of calves might reduce human infection risk.

/pdf/acute-middle-east-respiratory-syndrome-coronavirus-infection-25gc50vjto.pdf

Acute Middle East Respiratory Syndrome Coronavirus Infection in Livestock Dromedaries, Dubai, 2014

C. perfringens type A was isolated from different organs and intestines from breeding and racing camels which died from peracute and acute enterotoxemias in two separate outbreaks. Pathological changes in the digestive tract were mild in breeding camels, and severe in racing camels. A polyvalent clostridial antiserum of bovine origin given intravenously had a life-saving effect on breeding camels, but not on racing camels. In the two outbreaks, fifty percent of the breeding camels were suffering from an acute Trypanosoma evansi infection, and 25% of the racing camels had developed a salmonellosis. It is suggested that both infections played an important role as predisposing factors for the outbreak of C. perfringens enterotoxemias.

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Predisposing factors in enterotoxemias of camels (Camelus dromedarius) caused by Clostridium perfringens type A.

Between January and March 2001, eight 4- to 8-wk-old camels (Camelus dromedarius) from 2 farms from Dubai area of the United Arab Emirates were submitted for necropsy examination. The camels had diarrhea of 2-5 days duration. Grossly, a severe diphtheroid-to-hemorrhagic colitis was seen in all animals. Gamonts, unsporulated oocysts, sporulating oocysts, and fully sporulated oocysts were present in the intestinal epithelium and the lamina propria. Fully sporulated oocysts contained 2 sporocysts and 4 sporozoites in each sporocyst. Oocysts from fecal samples resembled oocysts of Isospora orlovi. This is the first report of an isosporan parasite associated with hemorrhagic enteritis in the large intestine of any animal.

Clinical large intestinal coccidiosis in camels (camelus dromedarius) in the united arab emirates: description of lesions, endogenous stages, and redescription of isospora orlovi, tsygankov, 1950 oocysts

Clostridium perfringens de type A a ete isole dans differents organes et dans l'intestin de jeunes dromadaires âges de 3 a 5 semaines, morts de necrose du muscle cardiaque. Aucun autre agent pathogene bacterien n'a ete isole. L'isolement de virus sur deux lignees cellulaires differentes, dont une culture de cellules cutanees foetales de dromadaire s'est egalement avere negatif. Les souris ayant recu des injections de filtrats depourvus de bacteries prepares a partir de contenus intestinaux de jeunes dromadaires autopsies sont mortes apres 1 a 6 h, revelant la presence de toxines clostridiennes. Nos resultats montrent que la necrose du muscle cardiaque est provoquee par les toxines de Clostridium perfringens de type A

/pdf/severe-heart-muscle-degeneration-caused-by-clostridium-4iqqrnlsom.pdf

Severe heart muscle degeneration caused by Clostridium perfringens type A in camel calves (Camelus dromedarius).

Background: Complicated intra-abdominal infections have become a major health challenge that merits safe and efficacious therapy. Antibiotic therapy is the treatment of choice, however the duration of antibiotic use is debatable. 
Objective: To compare the safety and efficacy of the short course and long course antibiotic therapy towards the treatment and the progressive outcome of patients presented with complicated intra-abdominal infections. 
Methodology: This comparative study was carried out on 94 subjects (chosen via non-probability, consecutive sampling), who presented with complicated intra-abdominal infections, had signs and symptoms of infection along with ultrasound abdomen examination consistent with infective foci and routine blood test showing raised total leukocyte count, at the Department of Surgery - Liaquat University Hospital, Hyderabad. Subjects were divided into two groups (47 in each) through a random assignments. Group-A was kept on a short course (5-7-days) while Group-B was kept on a long course (7-10 days) antibiotic therapy. Data were documented using a structured questionnaire, including inquiries related to sociodemographic details, disease specifics, and observed for the outcome variables (mainly postoperative early resolution of infection and long hospital stay). 
Results: In Group A, resolution of infection was achieved in 59.57%, 29.79% and 10.64% patients on day 5, 6 and 7, espectively. In Group B, esoluation of infection was only reported as 42.55%, 36.17% and 21.28% on day 5, 6 and 7, respectively. The median duration of taking antibiotic was almost half in short course group than the long. Surgical site infections were commonly observed in Group B patients. There was no mortality observed in both groups. There is no significance difference observed in primary outcome of clinical cure among the groups. 
Conclusion: It can be concluded that the short course antibiotic therapy has good efficacy to treat CIAI when the primary foci of infection are surgically extracted with adequate source control.

https://www.journaljpri.com/index.php/JPRI/article/download/35398/66858

Mansoor Ali

Papers

Acute Middle East Respiratory Syndrome Coronavirus Infection in Livestock Dromedaries, Dubai, 2014

Predisposing factors in enterotoxemias of camels (Camelus dromedarius) caused by Clostridium perfringens type A.

Clinical large intestinal coccidiosis in camels (camelus dromedarius) in the united arab emirates: description of lesions, endogenous stages, and redescription of isospora orlovi, tsygankov, 1950 oocysts

Severe heart muscle degeneration caused by Clostridium perfringens type A in camel calves (Camelus dromedarius).

Comparative Analysis of Short-Course Vs Long Course Antibiotic Therapy among Patients with Complicated Intra-Abdominal Infections